NovoSeven Off-Label Use Raises Concerns

Off-label use of NovoSeven (rFVIIa), a blood clotting drug approved for use in hemophiliacs, could be extremely dangerous, according to two new studies published in the Annals of Internal Medicine. Yet despite potential risks and questionable benefits, the same studies found that off-label NovoSeven use has grown enormously over the past several years.

NovoSeven, manufactured by Danish pharmaceutical company Novo
Nordisk, was released on the market in 1999 after gaining fast-track approval from the U.S. Food & Drug Administration (FDA). The drug is approved to prevent episodes of potentially fatal bleeding in patients with certain forms of hemophilia or congenital deficiencies in the protein. However, it is frequently used off-label to treat other conditions, including body and brain trauma, intracranial hemorrhage, aortic aneurysm, and in connection with cardiovascular surgery, neurosurgery and cancer and stem cell transplants.

Even though it is approved for a relatively small patient population, use of NovoSeven has soared in recent years, mostly because of off-label use. According to Dow Jones Newswire, from 2000 to 2008, the off-label use of NovoSeven in U.S. hospitals increased more than 140-fold. By 2008, 97% of all uses were off-label, according to one study.

The Annals of Internal Medicine studies examined the in-hospital use of NovoSeven in intracranial hemorrhage, cardiac surgery, trauma, liver transplantation and prostatectomy – all off-label indications. Neither study found any evidence that use of NovoSeven in any of the five indications improved patients’ mortality rates. What’s more, the studies found that NovoSeven increased the risk for thromboembolism when it was used in for cardiac surgery and intracranial hemorrhage.

“We found no evidence to suggest that the drug saves lives for any of the patient scenarios or conditions that we evaluated,” Veronica Yank, a fellow at Stanford University School of Medicine’s Prevention Research Center and a co-author on both reports, said according to The Wall street Journal.

An editorial accompanying the studies asked whether “improper” marketing may have contributed to the surge in off-label use of NovoSeven. “There is reason to wonder how the use of an obscure recombinant coagulation factor marketed exclusively to hematologists came to be used so widely by cardiac surgeons, neurologists and trauma specialists,” the authors of the editorial write.

For its part, Novo Nordisk denies any wrongdoing in the marketing of NovoSeven, and maintains it has cautioned doctors about it.

“It will never be our responsibility to control and regulate the off-label use. What we can do is never to promote it, which we have never done,” Novo Nordisk executive vice president and chief science officer, Mads Krogsgaard Thomsen, told Dow Jones Newswires.